Respectful Insolence

“Early detection of cancer saves lives.”

How many times have you heard this statement or something resembling it? It’s a common assumption (indeed, a seemingly common sense assumption) that detecting cancer early is always a Very Good Thing. Why wouldn’t it be, after all? For many cancers, such as breast cancer and colon cancer, there’s little doubt that early detection at the very least makes the job of treating the cancer easier. Also, the cancer is detected at an earlier stage almost by definition. But does earlier detection save lives? Does finding more disease before surgery that wouldn’t have been found before improve outcomes and survival rates?

In the case of breast cancer, a new imaging modality has brought this question to the fore in a pretty contentious way. If there’s one thing about treating cancer, there is always the push, both philosophical and technological, to find ever smaller pockets of tumor. I wrote about this very issue in great detail a while ago, explaining why ever earlier detection is not always the good thing that most people assume that it is, thanks to lead time bias, length bias, and the Will Rogers effect. The main reason that ever earlier and more sensitive tests to detect cancer are not an unalloyed good is primarily the phenomenon of overtreatment that they often cause, which occurs when small malignant lesions that would never have progressed to life-threatening cancer are treated as though they were cancer. The reason it is so hard to resist overtreatment when such lesions are found is because we have no reliable means of predicting which lesions will progress to cancer. Consequently, patients are subjected to what is in retrospect unnecessary surgery

Other than prostate cancer, nowhere does the impetus towards ever more sensitive tests to detect cancer bump into the fear of overtreatment is the debate over the use of MRI for breast cancer screening and for assessing the extent of disease prior to definitive surgery. Indeed, I’ve written about this issue before at least twice as well. Recently, I learned of a study that suggests that my fears about the increasing use of MRI might have turned out to be true. Here’s what I said:

Another issue to consider is an unintended consequence that is likely to come about if MRIs are done for all patients with breast cancer. For this discussion, remember the term “stage migration.” Most doctors are not going to order an MRI on just the opposite breast in a patient with newly diagnosed cancer. Indeed, prior to the publication of this paper, there was a growing tendency to order MRI for breast cancer to evaluate the extent of disease in the involved breast. That means that these patients are probably all going to get bilateral breast MRI, and this is where the problem of the extreme sensitivity of MRI comes in. There is little doubt that MRI will be more likely to find additional suspicious lesions in the breast with the known cancer an/or to indicate that the cancer goes further than it appears on mammography. As I asked a few days ago (rhetorically, of course), how can this not be good thing? Trust me, there’s a way. One unintended consequence of using MRI willy-nilly to evaluate extent of disease in breast cancer could well be an increase in the percentage of breast cancer patients undergoing mastectomies as opposed to lumpectomies.

What is important to remember here is that the survival rates for patients undergoing lumpectomy and radiation are the same as those for patients undergoing mastectomy. It is true that patients undergoing lumpectomy have a higher rate of local recurrence in the treated breast, but there is no survival difference because those recurrences can be salvaged with mastectomy. Also remember that these results have been validated over three decades with large clinical trials using the “primitive” technology of mammography and ultrasound, along with clinical assessment, as the only means of preoperative assessment of extent of disease in the affected breast. There is no evidence yet that preoperative MRI in any way leads to improved survival in breast cancer. However, there is evidence suggesting an unintended consequence of the increasing infiltration of MRI into the preoperative evaluation of women with breast cancer.

I’m referring to an abstract of a study that is scheduled to be presented in a week and a half at the American Society of Clinical Oncology (ASCO) meeting in Chicago, probably the largest meeting of clinical and academic cancer physicians and researchers in the world, with some 20,000 descending on the Windy City to soak up the latest results of cancer clinical trials. It’s definitely a talk that I will have to make an effort to attend, Trends in mastectomy rates at the Mayo Clinic Rochester: Effect of surgical year and preoperative MRI, a study which after the public release of abstracts to be presented at the meeting has been reported in the news thusly:

Signaling the reversal of a long decline in the use of mastectomy for breast cancer patients, a new study indicates more women are opting for the operation in part because more patients are getting MRI scans that can find additional tumors.

The marked change in care in recent years suggests a deepening of the emotional dilemma that many women face when choosing between mastectomy and more targeted treatments that can preserve the breast.

The study of 5,463 Mayo Clinic breast cancer patients found an increase of 13 percentage points in the use of mastectomy between 2003 and 2006. That rise coincided with a doubling in the use of MRI for such patients, according to the report, which was released Thursday in connection with an American Society of Clinical Oncology meeting to be held in Chicago later this month.

The rebound in mastectomy rates is sparking a debate among oncologists about whether the enhanced sensitivity of MRI, or magnetic resonance imaging, is always a good thing.

Indeed it is. In fact, because there was no strong evidence supporting its use preoperatively and because I believed that nonselective use of preoperative MRI would lead to a lot of overtreatment in the form of mastectomies, it was a long time before I finally caved in as a result of the pressure placed on clinicians by this study and acquiesced to the trend. Now, depending on the quality of the evidence presented in the Mayo Clinic abstract, there may be some ammunition to argue that the routine use of MRI may not be always be justified in the preoperative evaluation of cancer:

In a multivariate model adjusted for age, stage, contralateral breast cancer, and density, both MRI (Odds Ratio (OR): 1.7, p<0.0001) and surgical year (compared to 2003; OR: 1.4 for 2004, 1.9 for 2005, and 1.7 for 2006; p<0.0001) were independent predictors of mastectomy.

True, this is a correlative study, and correlation does not necessarily equal causation. However, inferring causation from this correlation is not unreasonable. The purpose of doing MRIs before surgery is to determine whether or not there are multiple tumors or extension of tumor beyond what can be seen on mammography or ultrasound. Because it is so sensitive, it will often find what it’s looking for. Once again, though, remember the Will Rogers effect and lead time bias. There may be evidence of extra disease there by MRI, but we know from mountains of data that using mammography and ultrasound alone to evaluate extent of disease has led to survival rates every bit equivalent of rates achieved with mastectomy. We also know from detailed pathological studies of mastectomy specimens that there is not infrequently microscopic tumor in the breast more than 2 cm away from the primary tumor. With a high rate of success, radiation “cleans” up any microscopic or tiny macroscopic foci of disease that weren’t included in the lumpectomy. It is unclear what adding MRI can do to improve upon this, but it is quite clear what preoperative MRI can do to influence a clinician’s and woman’s decision. If there is more extensive disease than thought, or if there are additional foci of possible disease (remember, without a biopsy it can’t be concluded that what the additional “spots” are in fact tumor), then often the surgeon has little choice but to recommend a mastectomy. As Dr. Seema Khan puts it:

In some cases, the additional tumors that MRI reveals might be effectively treated with more limited therapies, such as removing the initial lump followed by radiation and hormone treatment, said Dr. Seema Khan, director of the program for early detection and prevention of breast cancer at Northwestern Memorial Hospital. But once a scan uncovers additional tumors, many patients instinctively opt for a full mastectomy.

“There’s a huge question of whether we’re being led down a path of overtreatment by routinely using MRI,” said Khan, who was not part of the Mayo research team.

This is, of course, what I’ve been saying and thinking for some time, ever since MRI became increasingly pervasive. Even now, I (and every other surgeon who treats breast cancer) continue to grapple with the question of what the appropriate role of MRI is. Clearly more studies are needed to clarify the situation, but what do we do in the meantime while those studies are being done? What do we recommend to the women who are our patients? There’s no doubt that MRI is useful in women with a high risk of developing cancer due to family history or BRCA mutations. It also appears to be true that preoperative MRI is useful in young women with dense breasts who develop cancer. Moreover, we as surgeons focus on overall survival rates and forget that a local recurrence in the breast can be devastating to women, even if it is ultimately successfully treated. There are women who would rather sacrifice their breast to decrease the risk of local recurrence to very low levels (it’s never zero) even fully understanding that it won’t increase their chance of long term survival. It’s an individual decision, but the overdiagnosis that MRI can produce is a powerful force pushing women to have mastectomies.

One thing that somewhat confounds this study, though, is that there was a trend towards more mastectomies in women who did not undergo MRI. True, MRI emerged as an independent predictor of mastectomy in a multivariate analysis, but the study isn’t bulletproof. For one thing, in my own anecdotal experience, for reasons that are unclear to me, more women with breast cancer seem to choose mastectomy than before. This could be confirmation bias speaking on my part, but this study suggests that maybe it isn’t. The reason for this increasing preference for mastectomies is not clear to me at all, but there does seem to be a belief out there that somehow doing more surgery will make a cure more likely. I won’t pretend that this belief isn’t shared among some surgeons, evidence be damned.

What this study and the ongoing controversy over the proper role of MRI in the preoperative evaluation of breast cancer is that in cancer, increased sensitivity to detect ever smaller foci of cancer always comes with a price. Always. The benefit is that it can detect disease that may not have been detected on other imaging modalities before, allowing for treatment of the tumor before it becomes advanced. There are cancers that simply do not show up well on mammography or ultrasound until they are quite large. The price, of course, is overdiagnosis and over treatment. The difficult challenge we as clinicians and scientists have is to figure out the proper balance between the two and exactly when the use of this new technology is likely to produce the best chance of survival at the least cost.

After I’ve heard talk, perhaps I’ll comment further.

Comments

  1. #1 vlad
    May 21, 2008

    What’s wrong with using MRI as a screen and tag tool. MRI detects an currently non cancerous lesion. Tag the location on the patients medical files, preferably in digital form. On the next routine screening or 6 months later check the same lesion. This way if it becomes cancerous it can be removed. We can then get a better idea of the progression of lesions to tumors. We may be able to with all the medical data determine what about a given lesion makes it cancerous, if the feature that causes lesion to become cancerous (can’t remember the name) has physical manifestations.

    MRI’s are beautifully sensitive pieces of equipment but we don’t know how to use them in differentiating potentially cancerous lesions from benign ones. We need to do more research into lesion morphology under the MRI.

  2. #2 Orac
    May 21, 2008

    What’s wrong with using MRI as a screen and tag tool. MRI detects an
    currently non cancerous lesion. Tag the location on the patients medical
    files, preferably in digital form. On the next routine screening or 6
    months later check the same lesion.

    Nothing at all, if you’re using MRI for screening rather than the preoperative assessment of disease extent. Indeed, we already do something like this with mammography and ultrasound, with the ubiquitous six month followup exam for not clearly benign lesions. However, we have decades of experience with mammography to guide us in deciding which lesions can be safely followed that way and which cannot. Unfortunately, there is no comparable dataset for MRI because the technology is much newer than mammography.

    The problem with using such a technique for the situation that is the main topic of the post, the preoperative evaluation of breast cancer, is that it’s not advisable to wait six months to do a repeat image if a patient has a diagnosis of breast cancer and another area lights up in the breast. The main tumor that we know about will continue to grow. When that happens there are in essence three choices, some or all of which will apply depending on the location of the MRI lesion and whether it can be seen on ultrasound or mammography (usually they can’t; if they could then they would have been picked up by mammography or ultrasound): (1) do an MRI-guided needle core biopsy the area and potentially delay surgery; (2) just go straight to mastectomy under the assumption that the lesion is another focus of cancer; or (3) do a surgical biopsy of the other area at the time of lumpectomy and accept that you might have to come back and do a mastectomy if the area is positive.

    Lots of women (and surgeons) are choosing #2, hence the problem.

  3. #3 Calli Arcale
    May 21, 2008

    I would think that a lot of women might choose #2 merely because it is the most expedient option. Breast cancer (or any cancer) is a frightening thing to contemplate, and mastectomy offers the chance of getting it all taken care of in one fell swoop. It’s related to why more people are getting both knees replaced at once, rather than doing one and then doing the other one a year or two later. Sure, the recovery is worse if you do ‘em both, but at least you only have to go through it once.

  4. #4 bug_girl
    May 21, 2008

    Speaking as a large breasted woman that is tortured annually with mammograms–the appeal of MRI is obvious to me. I agree, though, that it is not without risks, especially since its use on breasts is still relatively new.

    Additionally, having seen my sister’s experience with reconstruction after cancer…yeah, I’d go with total mastectomy, for sure. I suspect that the hi mastectomy rate is an emotional response, not a medical recommendation.

  5. #5 Mariah
    May 21, 2008

    Funny, I was just talking today with my doctor about my upcoming mammogram in two weeks. They ordered this one for 6 months since the last, because of something they saw in the last one.

    With my mother dead from breast cancer, and my sister’s run-in with it, and the same issues as bug girl above, I would get mastectomy too.

    I’m not actually using my breasts for anything except holding up my clothes. And for years now I have been convinced that they are plotting to kill me within the next 10 years.

    So how much is the peace of mind worth over the next 40+ years that I hope for my lifespan? I don’t know. But it is worth more than a couple of hangers.

  6. #6 synapse
    May 21, 2008

    I’ve read in the popular press that increasing numbers of women are choosing to have prophylactic mastectomies, because they test positive for a cancer-promoting BRCA mutation and don’t want to worry about cancer ever. It’s possible that women are changing their attitudes towards breasts and are more willing to part with them in order to avoid extra inconvenience and worry.

  7. #7 Marilyn
    May 21, 2008

    I was diagnosed with early stage breast cancer in June 2007. I had a lumpectomy and radiation. My Oncotype score was 5 (I’m on tamoxifen).

    Last week I was at my GYN for my annual visit and he recommended that I get an MRI instead of a mammogram. My oncologist didn’t have an opinion. The surgeon said to get a mammogram.

    Do you have any thoughts? I realize this is not the subject of your post. (I did have a preoperative MRI, which didn’t find anything.)

    I have dense breasts, FWIW.

    Thanks, Marilyn

  8. #8 Tracy W
    May 21, 2008

    Is breast cancer any more common than anywhere else cancer? I mean, is the body more likely to develop breast cancer than a tumour somewhere else?

  9. #9 Mariah
    May 21, 2008

    You know, I was just thinking more about this, and another reason I would consider mastectomy right away is because I currently have health insurance. I have no idea if I will have it later. Or if I will be tagged with a “pre-existing condition” like my sister has been.

    Who knows if I will have insurance in 5 years?

  10. #10 Beth Nichols Boyd
    May 21, 2008

    I underwent a mastectomy as a consequnce of having an MRI. Each situation is different Let me briefly tell you mine:

    After experiencing a “burning” feeling in my breast, I underwent both a mammogram and then an ultrasound, which showed nothing unusual. My surgeon told me to go home, but I persisted and inquired about an MRI (this was more than 3 years ago, when this technology was not perhaps as well known by the average woman, as it appears to be today). My surgeon told me that it was unnecessary. I had the MRI done, against his advice, and my cancer showed up like a neon sign – even I could recognize it from half a room away. It was “just DCIS”, but the ensuing 5 cm. biopsy failed to obtain a clear margin and I chose to have a mastectomy (done by a different surgeoun, thank you), of the affected breast only.

    I was given the option of a lumpectomy with follow-up radiation, as you mentioned: “With a high rate of success, radiation “cleans” up any microscopic or tiny macroscopic foci of disease that weren’t included in the lumpectomy.” Of concern to me, since I was in my 40′s (with a few more decades to go, I hope), were the long-term consequences of lumpectomy-following radiation, about which there seems to be little long-term information.

    It was a very difficult decision and one that I reached after extensive research. I still think it was in the best interest of my long-term survival.

    Your comment,” It is true that patients undergoing lumpectomy have a higher rate of local recurrence in the treated breast, but there is no survival difference because those recurrences can be salvaged with mastectomy”, tells the story for me. This is, unfortunately, a cancer and a surgery with both physical and significant psychological implications and to suggest that women might be better off waiting for the next recurrence, or undergoing a “salvage” mastectomy once their cancer has recurred, does not seem to me to be clearly in their best overall (physical + psychological) interest. (As an aside: I certainly don’t know the figures, but every surgery involves both anesthesia and post-operative infection risks – why double that?)

    I understand your arguments, believe me, but having undergone this nightmare, I am at least grateful that I had the best information available to me, at the earliest opportunity. What one does with that information is up to the patient and her surgeon, but I do not agree that this is a situation where more information is deleterious.

    I read your column regularly and I realize that you can be merciless with those whom you disagree, and that is your prerogative, but I think my experience is pertinent; in this case, more information was not a bad thing.

  11. #11 Orac
    May 21, 2008

    This is, unfortunately, a cancer and a surgery with both physical and significant psychological implications and to suggest that women might be better off waiting for the next recurrence, or undergoing a “salvage” mastectomy once their cancer has recurred, does not seem to me to be clearly in their best overall (physical + psychological) interest.

    That’s not what I was suggesting at all, nor was I in any way heaping contempt on anything. (Really, did you see me use my favorite “burning stupid” catchphrase anywhere?) I was merely describing the unintended consequences of more sensitive new technology. Similar new consequences were seen with the addition of PSA screening for prostate cancer, and only now are surgeons starting to “back off” a bit.

    But let me elaborate a bit. First off, the local recurrence rate with radiation for a good lumpectomy with clean margins and radiation should be well under 10%. Second off, contrary to what is commonly believed mastectomy does not reduce the local recurrence rate to zero. The problem I’ve been seeing is that women with fairly small tumors that without MRI would be clearly amenable to lumpectomy and radiation using preoperative mammography and ultrasound end up getting an MRI and finding questionable other areas, resulting in their decision to undergo a mastectomy. Most of the time, that was probably overtreatment. Indeed, for some smaller tumors, there is a trend to use partial breast irradiation, which allows for repeat lumpectomy and radiation in the event of a recurrence. The data supporting this are not mature, but early results are promising.

    The choice is obviously individualized; there is no real “right” answer, at least in terms of data. However, doing a mastectomy for small tumors that could be treated with lumpectomy strikes some of us as overkill, given how far we’ve come from the days of radical mastectomy as recently ago as the 1970s. Nowadays, early stage breast cancer can often be cured with relatively little morbidity; it’s disconcerting to see uncertainty due to a new technology cause us in a way to “turn back the clock.” Moreover, a mastectomy and reconstruction hold the risk for more complications than a “salvage” mastectomy that would only be necessary maybe 8% of the time. There are risks to choosing mastectomy over lumpectomy as well. No choice is without its upside and downside, and this rush to adopt MRI may be skewing the decision on uncertain data. That’s all I was saying.

  12. #12 vlad
    May 22, 2008

    “I had the MRI done, against his advice, and my cancer showed up like a neon sign – even I could recognize it from half a room away.” Did they actually biopsy the tissue after the mastectomy? It could have been almost anything. My wife had a buring in her breast and jack shit showed up on the mamogram. Had she had an MRI the abscess (which is all she had) would have lit up like a Christmas tree doused in gasoline. She was too young and had little family history. I love that imaging modality but it’s limits are based on those interpreting them and how the scan is set up.

  13. #13 BNB
    May 22, 2008

    “Did they actually biopsy the tissue after the mastectomy?”
    No duh – it was just a guess. (Your question seeems breathtakingly patronizing to me. I’m sorry if my response seems inappropriate. I don’t mean to sound dramatic, but the entire process was traumatic to me.)

    The surgery was done at the Mayo Clinic in Arizona. (The original surgeon who suggested that it was “all in my head” was not with the Mayo Clinic). And yes, multiple pathology reports were done following both the biopsy and the subsequent mastectomy. “Extensive DCIS… with focal central necrosis.”

    No woman would lightly choose to have her breast cut off. I’m glad that your wife had only an abscess.

    As I said in my original comment, I am grateful that the best information was available to me.

  14. #14 vlad
    May 22, 2008

    “Your question seeems breathtakingly patronizing to me. ” Was not my intent.

    “No duh – it was just a guess.” They don’t always do it though they should.

    There are a lot of imaging screw ups that can if not properly investigated lead to mistakes. In your case it wasn’t. Needless mastectomies are bad for everyone involved.

    I’m pushing for making sure that medical personnel use more imaging and less surgery. MRI is new for this and requires completely different approach and training.

  15. #15 AnnR
    May 22, 2008

    In my travels in breast cancer support groups I’ve very rarely met anyone who regretted they were over-treated. Now this could be because of the self-selecting nature of support groups, or it could be because many women have had a friend/relative who’se had breast cancer and they’re grateful that they’re going to miss out on it.

    There is no reasoning with someone who could have a lumpectomy but can’t relax with that idea and wants a mastectomy. So in my view the important thing is that every woman have a choice.

    Since MRI and other imaging is expensive, and generates needless expense/anxiety for benign tests/biopsies we probably need the profession to have some standard for when they’re really needed because there probably are better uses of resources in the medical realm. That’s a big issue across our entire health care system, not easily dealt with.

  16. #16 laurasf
    May 22, 2008

    My onc wants an MRI every year because my 41 year old breasts are very dense and I had both invasive and lobular cancer, the later of which is easily missed by mammogram. However, with my out of pocket costs being $1,500 for my last MRI (yes, I have insurance: blue cross PPO), I told my doc that from now on I’ll take my chances with mammogram.

    I had to have a mastectomy because I had multi focal disease with invasive cancer spread all over the breast. I was told that there was no medical reason to do anything with the other breast. In hindsight, I wish I had done a bilateral mastectomy, as I would have had a MUCH better cosmetic result, plus I wouldn’t have to do this yearly scanning. It would have saved me a ton of money in the long run. And now that I can no longer afford yearly MRI, I worry that the lobular cancer will return.

  17. #17 Terri
    May 22, 2008

    Having just had a mastectomy, after a “failed” lumpectomy w/o clean margins, and the appearance of multifocal breast cancer, I think the lumpectomy vs. mastectomy mindset assumes too many clearly defined cases.

    In real life things don’t work out quite so nicely.

    I had a mammogram and ultrasound which showed nothing. I had a preoperative(lumpectomy) MRI which showed a couple of suspicious lesions. They weren’t sure if it was scar tissue from my biopsy or cancer. Turned out to be cancer…and not only that, but when they did the lumpectomy, there was more of it than had shown up on the MRI.

    When tests have proven to be wrong over and over again, and patients get pathology results and outcomes that don’t line up with statistics, it’s little comfort to be reassured by a surgeon that “studies show” one thing or another.

    Studies cram a lot of information into digestible bites that don’t always conform to a particular patient’s case. I would say that most of these decisions are not made lightly.

  18. #18 Samantha Vimes
    May 23, 2008

    Lumpectomy + radiation vs. Mastectomy– does the mastectomy come with radiation, too? If not, right there, could be the reason women would rather just take the whole thing off. Or even if the followup treatment is the same, your talking about months of wondering if other lumps will turn up in the same breast, meaning a second surgery which would be the mastectomy. And you can’t imagine why a woman would just want it gone?
    Breasts aren’t testicles. They don’t create the hormones that make us feminine. They serve no purpose, if one is not nursing a baby. And they are fairly routinely being replaced… by ones women choose, rather than what nature gave.
    I have a friend who is just finishing up her chemo treatment. Her family history suggested her breast cancer would be aggressive, and she had lumps in both. She’s been wishing for a breast reduction for years– so she was able to make arrangements for smaller implants to take the place of her real breast tissue all in one surgery with the mastectomy. It wasn’t without problems, but it was a very good thing for her, and I thought I might do the same if I ever get breast cancer. Quite possibly this is mostly a reaction of women with large/dense breasts who find the big weights that aren’t good for our spines a bit of a problem anyhow… but I just want you to bear in mind that there are a certain percentage of women for whom “lop ‘em off” would be an easy choice, even without an MRI to encourage it.

  19. #19 terri
    May 24, 2008

    I know this is a late comment, but I wasn’t sure if someone already addressed this.

    The stats are the same with lump and rads as mastectomy, but who is keeping track of how many of those lums and rads eventually became mastectomies because of a reoccurance? That would explain why overall survival is the same.

    A woman gets a lumpectomy and rads, has a local reccurance and must have a mastectomy because you can’t radiate twice. The cancer is treated again, keeping its stats equal with the “only mastectomy” group…yet a woman has had to go through mulitple treatments.

    Has that been considered in these stats?